Therapeutic vaccine based on aDC1 dendritic cells pulsed with inactivated autologous virus for the control of viremia after ATI in HIV infected individuals

• Grant number: 16/25212-9
• Support Opportunities: Research Projects - Thematic Grants
• Start date: June 01, 2018
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Alberto José da Silva Duarte
• Grantee: Alberto José da Silva Duarte
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Luís Fernando de Macedo Brígido
• Associated researchers: Alessandra Pontillo ; Alexandre de Almeida ; Ana Paula Rocha Veiga ; Bosco Christiano Maciel da Silva ; Bruna Tereso Santillo ; Luanda Mara da Silva Oliveira ; Maria Notomi Sato ; Maria Rita Polo Gascón ; Paula Ordonhez Rigato ; Robbie B. Mailliard ; Rosana Coura Rocha ; Telma Miyuki Oshiro Sumida ; Thales Jose Bueno Polis
• Associated scholarship(s): 24/15230-6 - Effect of different freezing media on cell viability for use in immunotherapy protocols, BP.IC; 24/17424-2 - Therapeutic vaccine based on ¿DC1 dendritic cells pulsed with inactivated autologous virus for the control of viremia after ATI in HIV infected individuals, BP.TT; 24/15784-1 - Characterization and loading of relevant HIV antigens onto aDC1 dendritic cells for anti-HIV immunotherapy, BP.TT; + associated scholarships 23/11990-3 - Production and characterization of polarized dendritic cells aDC1 for use in anti-HIV immunotherapy, BP.TT; 22/06813-2 - Therapeutic vaccine based on alphaDC1 dendritic cells and viruses inactivated autologous targeting viral control of HIV-1 infected individuals discontinuing antiretroviral therapy, BP.TT; 22/04994-0 - Evaluation of yield and viability of aDC1 polarizing dendritic cells used in an anti-HIV immunotherapy assay, BP.IC; 19/24849-1 - Nanoparticles as HIV antigen delivery: potential application in anti-HIV immunotherapy using monocyte-derived dendritic cells, BP.DR; 21/06139-7 - Caracterization and loading of HIV-relevant antigens in dendritic cells aDC1 for anti-HIV immunotherapy, BP.PD; 19/07976-0 - Obtaining, characterization and loading of autologous virus by aDC1 dendritic cells for immunotherapy anti-HIV, BP.PD; 19/02948-8 - Therapeutic vaccine based on aDC1 dendritic cells pulsed with inactivated autologous virus for the control of viremia after ATI in HIV infected individuals, BP.TT; 18/12460-0 - Production and characterization of polarized dendritic cells aDC1 for use in anti-HIV immunotherapy, BP.PD - associated scholarships

Abstract

Dendritic cell based immunotherapy is a potential tool to stimulate a specific immune response, as a complementary treatment for HIV-infected individuals using ART. Polarizing DCs are capable to produce high levels of IL-12p70 and induce a strong cytotoxic response that is very useful in viral infections. In this context, we propose to study aDC1 pulsed with autologous inactivated virus for treatment of HIV infected individuals. The study will include 30 diagnosed HIV-infected patients not ART treated at inclusion time. Six months after treatment initiation they will be immunized or not with aDC1 according to the arms of this study: G1) placebo control/without ART interruption; G2) aDC1immunization/without ART interruption; G3) aDC1 immunization/analytical treatment interruption. Autologous PBMCs will be collected for virus isolation and patients will start ART. Waiting for 24 weeks for PVL going below detection, samples will be collected for baseline parameters and vaccine will be inoculated in 3 doses (with a fortnight interval). Three weeks after 3th vaccine inoculation, ART will be interrupted only for G3 patients. Patients will be followed for more 12 weeks and blood and biopsis (jejunum) samples will be collected for different parameters measurement as immune activation, immunogenecity, humoral response, mucosal cellular immunity and virologic profile and viral reservoir analysis. (AU)

Scientific publications

(9)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TIYO, BRUNA T.; SCHMITZ, GABRIELA J. H.; ORTEGA, MARINA M.; DA SILVA, LAIS T.; DE ALMEIDA, ALEXANDRE; OSHIRO, TELMA M.; DUARTE, ALBERTO J. DA S.. What Happens to the Immune System after Vaccination or Recovery from COVID-19?. LIFE-BASEL, v. 11, n. 11, p. 21-pg., 2021-11-01. (16/25212-9, 21/06139-7, 18/12460-0)

ORTEGA, MARINA MAZZILLI; DA SILVA, LAIS TEODORO; CANDIDO, ERIKA DONIZETTI; ZHENG, YINGYING; TIYO, BRUNA TIAKI; FERREIRA, ARTHUR EDUARDO FERNANDES; CORREA-SILVA, SIMONE; SCAGION, GUILHERME PEREIRA; LEAL, FABYANO BRUNO; CHALUP, VANESSA NASCIMENTO; et al. Salivary, serological, and cellular immune response to the CoronaVac vaccine in health care workers with or without previous COVID-19. SCIENTIFIC REPORTS, v. 12, n. 1, p. 12-pg., 2022-06-16. (18/12460-0, 16/25212-9, 21/06139-7, 19/24849-1, 20/06409-1, 14/50489-9)

CABRAL, GABRIELA BASTOS; AHAGON, CINTIA MAYUMI; DE SOUZA GUIMARAES, PAULA MORENA; SILVA LOPEZ-LOPES, GISELLE IBETTE; HUSSEIN, IGOR MOHAMED; CILLI, AUDREY; ALVES, IVY DE JESUS; COELHO BOMBONATTE, ANDREA GOBETTI; SAMPAIO TAVARES TIMENETSKY, MARIA DO CARMO; DA SILVA SANTOS, JAQUELINE HELENA; et al. se of Sanger protocols to identify variants of concern, key mutations and track evolution of SARS-CoV-. Journal of Virological Methods, v. 300, FEB 2022. (16/25212-9, 18/14384-9)

DA SILVA, LAIS TEODORO; TIYO, BRUNA TIAKI; MOTA, SILVIA DE JESUS; ORTEGA, MARINA MAZZILLI; SCHMITZ, GABRIELA JUSTAMANTE HANDEL; TANIWAKI, NOEMI NOSOMI; NISHINA, GISLENE MITSUE NAMIYAMA; DUARTE, ALBERTO JOSE DA SILVA; OSHIRO, TELMA MIYUKI. Effects of Injectable Solutions on the Quality of Monocyte-Derived Dendritic Cells for Immunotherapy. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2024, p. 11-pg., 2024-06-07. (19/24849-1, 23/11990-3, 18/12460-0, 14/50489-9, 16/25212-9)

DA SILVA, LAIS TEODORO; SANTILLO, BRUNA TERESO; DE ALMEIDA, ALEXANDRE; DA SILVA DUARTE, ALBERTO JOSE; OSHIRO, TELMA MIYUKI. Using Dendritic Cell-Based Immunotherapy to Treat HIV: How Can This Strategy be Improved?. FRONTIERS IN IMMUNOLOGY, v. 9, DEC 18 2018. (18/12460-0, 16/25212-9)

DA SILVA, LAIS TEODORO; ORTEGA, MARINA MAZZILLI; TIYO, BRUNA TIAKI; TABOSA VIANA, ISABELLE FREIRE; DE LIMA, TAYNA EVILY; TOZETTO-MENDOZA, TANIA REGINA; DA SILVA OLIVEIRA, LUANDA MARA; EMIDIO TEIXEIRA, FRANCIANE MOURADIAN; LINS, ROBERTO DIAS; DE ALMEIDA, ALEXANDRE; et al. SARS-CoV-2 recombinant proteins stimulate distinct cellular and humoral immune response profiles in samples from COVID-19 convalescent patients. Clinics, v. 76, 2021. (18/12460-0, 16/25212-9)

LUANDA MARA DA SILVA OLIVEIRA; BRUNA TIAKI TIYO; LAIS TEODORO DA SILVA; LUIZ AUGUSTO MARCONDES FONSECA; ROSANA COURA ROCHA; VERA APARECIDA DOS SANTOS; CARINA CENEVIVA; ANDERSON APARECIDO BEDIN; ALEXANDRE DE ALMEIDA; ALBERTO JOSÉ DA SILVA DUARTE; et al. Prevalence of anti-SARS-CoV-2 antibodies in outpatients of a large public university hospital in Sao Paulo, Brazil. Revista do Instituto de Medicina Tropical de São Paulo, v. 62, 2020-11-13. (16/25212-9, 19/07976-0, 18/12460-0)

DA SILVA, LAIS TEODORO; ORTEGA, MARINA MAZZILLI; PERAZZIO, SANDRO FELIX; OSHIRO, TELMA MIYUKI; DA SILVA DUARTE, ALBERTO JOSE; CARNEIRO-SAMPAIO, MAGDA. Anti-SARS-CoV-2 reactive T cells in a XLA patient after CoronaVac vaccine. JOURNAL OF CLINICAL IMMUNOLOGY, v. 42, n. SUPPL 1, p. 2-pg., 2022-04-01. (16/25212-9, 14/50489-9)

OSHIRO, TELMA MIYUKI; DA SILVA, LAIS TEODORO; ORTEGA, MARINA MAZZILLI; PERAZZIO, SANDRO FELIX; DA SILVA DUARTE, ALBERTO JOSE; CARNEIRO-SAMPAIO, MAGDA. Patient with agammaglobulinemia produces anti-SARS-CoV-2 reactive T-cells after CoronaVac vaccine. Clinics, v. 77, p. 2-pg., 2022-01-01. (16/25212-9, 14/50489-9, 18/12460-0)